DESCRIPTION: (Applicant's abstract) Neonatal brain injury remains a major cause of morbidity and mortality for premature infants. This injury includes periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH) with or without intraparenchymal hemorrhage (IPH). Recently, diffusion-weighted imaging (DWI) has proven to be an extremely sensitive and early indicator of brain injury following a variety of insults. We propose to apply quantitative measurements of diffusion and diffusion anisotropy to evaluate the timing, extent, and pathophysiology of this rather complex spectrum of injury as a step towards developing therapies to prevent and/or treat it. We will establish normal values for diffusion parameters for preterm new born infants. We will also determine the timing and magnitude of the changes of these parameters in association with brain injury by studying infants born following asphyxial brain injury due to a tight nuchal cord at birth. These infants were chosen because the timing of the injury is well known in this case. We will obtain diffusion MRI scans at birth in infants who subsequently develop PVL. These images will be analyzed to determine whether this injury is typically present before birth or occurs after birth. Finally, we will obtain diffusion MRI scans on infants following IVH to determine whether there is evidence of widespread injury due to venous infarction.